1. Technical Field of the Invention
The present invention relates to novel melatonin derivatives having improved anti-free-radical (AFR) activity, and to topically applicable dermocosmetic compositions comprised thereof; the subject compositions are well suited for combating the clinical signs of human skin aging and/or for improving the appearance of the skin, the scalp or the hair.
2. Description of the Prior Art
Over the course of time, different signs and conditions appear on the skin and/or on the scalp and/or on the hair, which are very characteristic of aging, reflected, in particular, by a modification of the skin structure and functions.
The principal clinical signs of aging of the skin are, especially, the appearance of fine lines and deep wrinkles which increase or are accentuated with age. Moreover, the skin complexion is generally modified and diffuse irritations and occasionally telangiectasias may exist on certain areas of the skin. Another clinical sign of aging is the dry and coarse appearance of the skin, which is due essentially to more considerable desquamation. Lastly, a loss of firmness and tonicity of the skin are observed, which, as for the wrinkles and fine lines, is at least partly explained by dermal and epidermal atrophy, as well as by a flattening of the formation. It is thus observed that the clinical signs of aging of the skin result essentially from dysfunction of the principal biological mechanisms involved in the skin.
Free radicals are known factors responsible for the aging of cells, in particular the skin. They originate principally from molecular oxygen and are induced, for example, by atmospheric pollutants and/or by ultraviolet radiation.
The following free radicals are particularly representative:
(a) singlet oxygen, which is very oxidative, very toxic and has a very short lifetime, produced by the excitation of molecular oxygen by light photons;
(b) the superoxide anion radical, produced by the addition of an electron to oxygen and which enables the production of very reactive hydroxyl radicals;
(c) the hydroxyl radical, which is very oxidative and the most toxic to cells.
Also illustrative are lipoperoxide radicals which are the oxidation products of membrane lipids and extracellular iron, which, by reacting with hydrogen peroxide and the superoxide anion radical accumulated outside the cell, will promote the production of hydroxyl radicals.
Preventing or treating the damage caused on the skin, the scalp or the hair by free radicals, in particular aging of the skin, whether intrinsic or extrinsic aging, and the clinical signs indicated above, is essentially a matter of maintaining or improving the appearance of the skin, the scalp or the hair.
Various active agents have been described as possessing AFR properties, as well as their use in cosmetics. These are compounds such as tocopherols, for example vitamin E, which are known to possess both antioxidant properties with respect to the phospholipids of the cell membrane and anti-free-radical (AFR) properties (J. B. Chazan and M. Szulc, Cah. Nutr. Diet., 6 XXII--1, 66-76 (1987)) or superoxide dismutases, for example those extracted from bovine erythrocytes (Markovitz, J. Biol. Chem., 40, 234 (1959)), from Escherichia coli (Keele and Fridovich, J. Biol. Chem., 245, 6176 (1970)) or from marine bacterial strains (FR 73/13670), or, alternatively, melatonin.
Melatonin, or N-acetyl-5-methoxytryptamine, which is particularly well known for its circadian activity in regulating the production of hormones, is also indicated for its antioxidant activity (Reiter R. J., Verhandung der Deutschen Zoologischen Gesellschaft, 87 (2), 195-204 (1994); Reiter R. J. et al., Neuroendocrinoll Letter, 15 (1-3), 103-113 (1993); Reiter R. J. et al., J. Pineal Res., 18 (1), 1-11 (1995)), in particular its AFR activity (Reiter R. J. et al., Brazilian Journal of Medical and Biological Research, 26 (22), 1141-1155 (1993)). Melatonin has also been described for its dermocosmetic properties in order to improve the appearance of the skin (JP-61/221,104; U.S. Pat. No. 4,746,674), or to protect the skin against the effects of irradiation with UV rays (EP-0,438,856; E. Bangha et al., Dermatology 191, [2], 176 (1995)). Most of the studies on melatonin relate to the oxidation phenomena associated with aging of the brain (Poeggeler B. et al., J. Pineal Res., 14(4), 151-168 (193); Cagnoli C. M. et al., J. Pineal Res., 18 (4), 222-226 (1995); Melchiorri D. et al., Faseb J., 9 (12), 1205-1210 (1995); Sewerynek E. et al., Neuroscience Letters, 195 (3), 203-205 (1995)) and it appears that melatonin is more effective than common AFR active agents such as vitamin E (Pieri C. et al., Life Sciences, 55 (15), 271-276 (1994)).